The impact of protein-based pharmaceuticals in the treatment of disease continues to surge, driven by discoveries in genomics and successful implementation by the biotechnology industry. The production of proteins remains a challenge because of the increasing demand and need for large doses. Many proteins require post-translational modifications that are only efficiently synthesized by vertebrate cells. Vertebrate cells, such as the industry standard Chinese Hamster Cells (CHO), can be difficult to grow under GMP conditions and require immense resources to propagate at the scale needed to meet market demands. Animal and plant based bioreactors systems are an attractive alternative to CHO due to low maintenance costs and ease of scalability. However, the post-translational modification of biopharmaceuticals, in particular glycosylation, is executed differently in animals and plants as compared to CHO cells. The hen, because of its prolific egg laying and protein production abilities, has been pursued as a biopharmaceutical bioreactor. The sugar molecules attached to certain proteins produced in eggs of transgenic hens have been found to share the same basic structure with CHO and human proteins. However there are some structural elements that are lacking in the egg white-derived sugars that could be important for bioactivity and bioavailability in human patients. The goal of this project is to genetically engineer hens to impart wholly-human like sugar structures upon egg white-derived biopharmaceuticals. PUBLIC HEALTH RELEVANCE: The proposed project, creation of transgenic hens that produce human biopharmaceuticals with human-like characteristics, will be a major step in the maturation of a production technology that will have dramatic effects on the biopharmaceutical industry. In the near future, consumers will have access to the first generation of hen-produced drugs and will benefit from the greatly reduced cost as well as increased safety and efficacy of such drugs.